Tumor Microvasculature and Microenvironment: Novel Insights Through Intravital Imaging in Pre-Clinical Models
Article first published online: 29 MAR 2010
© 2010 John Wiley & Sons Ltd
Volume 17, Issue 3, pages 206–225, April 2010
How to Cite
FUKUMURA, D., DUDA, D. G., MUNN, L. L. and JAIN, R. K. (2010), Tumor Microvasculature and Microenvironment: Novel Insights Through Intravital Imaging in Pre-Clinical Models. Microcirculation, 17: 206–225. doi: 10.1111/j.1549-8719.2010.00029.x
- Issue published online: 29 MAR 2010
- Article first published online: 29 MAR 2010
- Received 1 December 2009; accepted 29 January 2010.
- intravital microscopy;
- stromal cells;
- vascular normalization
Microcirculation (2010) 17, 206–225. doi: 10.1111/j.1549-8719.2010.00029.x
Intravital imaging techniques have provided unprecedented insight into tumor microcirculation and microenvironment. For example, these techniques allowed quantitative evaluations of tumor blood vasculature to uncover its abnormal organization, structure and function (e.g., hyper-permeability, heterogeneous and compromised blood flow). Similarly, imaging of functional lymphatics has documented their absence inside tumors. These abnormalities result in elevated interstitial fluid pressure and hinder the delivery of therapeutic agents to tumors. In addition, they induce a hostile microenvironment characterized by hypoxia and acidosis, as documented by intravital imaging. The abnormal microenvironment further lowers the effectiveness of anti-tumor treatments such as radiation therapy and chemotherapy. In addition to these mechanistic insights, intravital imaging may also offer new opportunities to improve therapy. For example, tumor angiogenesis results in immature, dysfunctional vessels—primarily caused by an imbalance in production of pro- and anti-angiogenic factors by the tumors. Restoring the balance of pro- and anti-angiogenic signaling in tumors can “normalize” tumor vasculature and thus, improve its function, as demonstrated by intravital imaging studies in preclinical models and in cancer patients. Administration of cytotoxic therapy during periods of vascular normalization has the potential to enhance treatment efficacy.